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. 2017 Dec 13;18(12):2696.
doi: 10.3390/ijms18122696.

Clodronate as a Therapeutic Strategy against Osteoarthritis

Maria Teresa Valenti  1 , Monica Mottes  2 , Alessandro Biotti  3 , Massimiliano Perduca  4 , Arianna Pisani  5 , Michele Bovi  6 , Michela Deiana  7   8 , Samuele Cheri  9   10 , Luca Dalle Carbonare  11
Affiliations

Clodronate as a Therapeutic Strategy against Osteoarthritis

Maria Teresa Valenti et al. Int J Mol Sci. .

Abstract

Osteoarthritis (OA), the most prevalent musculoskeletal pathology, is mainly characterized by the progressive degradation of articular cartilage due to an imbalance between anabolic and catabolic processes. Consequently, OA has been associated with defects in the chondrocitic differentiation of progenitor stem cells (PSCs). In addition, SOX9 is the transcription factor responsible for PSCs chondrogenic commitment. To evaluate the effects of the non-amino bisphosphonate clodronate in OA patients we investigated SOX9 gene expression in circulating progenitor cells (CPCs) and in an in vitro OA model. We evaluated pain intensity, mental and physical performance in OA patients, as well as serum biomarkers related to bone metabolism. In addition, in order to improve therapeutic strategies, we assayed nanoparticle-embedded clodronate (NPs-clo) in an in vitro model of chondrogenic differentiation. Our data showed upregulation of SOX9 gene expression upon treatment, suggesting an increase in chondrocytic commitment. Clodronate also reduced osteoarticular pain and improved mental and physical performance in patients. Furthermore, NPs-clo stimulated SOX9 expression more efficaciously than clodronate alone. Clodronate may therefore be considered a good therapeutic tool against OA; its formulation in nanoparticles may represent a promising challenge to counteract cartilage degeneration.

Keywords: SOX9; clodronate; gene expression; osteoarthritis; progenitor cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SOX9 (A) and COL2A1 (B) fold of expression in CPCs of Normal Donors (NDs) and patients at baseline (M0), after 3 (M3) and 6 (M6) months. * p < 0.05; ** p < 0.001.
Figure 2
Figure 2
Effects of clodronate in mesenchymal stem cells (MSCs). SOX9 fold of expression in MSCs treated with and w/o clodronate in chondrogenic medium in the presence or absence of ILβ1 (A). SOX9 (B) and COL2A1 (C) fold of expression in chitosan and hyaluronic acid empty nano particles (NPs) or clodronate embedded nanoparticles in chindrogenic medium with or w/o ILβ1. The synergistic action of NPs and clodronate is noteworthy. * p < 0.05; ** p < 0.01.
Figure 3
Figure 3
Alcian blue staining. After 21 days of culture, cells were fixed and stained with alcian blue in order to evaluate GAGs production. Control (A), cells treated with GFP nanoparticles alone (B); in the presence of ILβ1 (C); clodronate embedded NPs in the presence of ILβ1 (D). Scale bar 150 μm; insert 80×.
See this image and copyright information in PMC

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